High-grade pre-cancerous anal lesions are
more likely to regress than progress, according to Australian research
published in the online edition of AIDS.
The study involved 574 men, three-quarters of whom were HIV positive. Only 1%
of patients progressed to anal cancer, compared to a regression rate of 24%.
“Our data provide reassurance that
high-grade ASILs [anal squamous intraepithelial lesions] diagnosed at any one
point are much more likely to spontaneously regress than progress to cancer,”
write the authors. “Not all patients with high-grade ASILs warrant treatment.”
Incidence of anal cancer has increased
among HIV-positive people, with rates highest among men who have sex with
men. Anal cancer is caused by persistent infection with high-risk strains of
human papillomavirus (HPV) and is preceded by a pre-cancerous phase of cell
changes called high-grade ASIL. This is divided into grade 2 or grade 3 anal
intraepithelial neoplasia (AIN2, AIN3). These diagnoses are often combined
together as high-grade anal intraepithelial neoplasia (HGAIN).
Investigators at St Vincent’s Hospital,
Sydney, were concerned that relatively little is known about rates of disease
progression and regression in people with HGAIN. However, they noted that high
rates of spontaneous disease regression have been observed in women with
cervical intraepithelial neoplasia. They hypothesised that this would also be
the case with high-grade ASILs. The investigators also hypothesised that the
likelihood of disease progression to HGAIN would be related to HIV infection
status and CD4 cell count.
They therefore designed a retrospective
study involving 570 men who had undergone an anal Pap smear or high-resolution
anoscopy between 2004 and 2011. Three-quarters of these men were HIV positive.
These HIV-positive participants had a median CD4 cell count of 500 cells/mm3
and 84% had an undetectable viral load.
Participants were followed for a median of one
A total of 152 people were eligible for
inclusion in the analysis of disease progression. Overall, 19 individuals
(12.5%) developed incident HGAIN over 256 person-years of follow-up. The
incidence of progression to HGAIN was 7.4 per 100 person-years. This did not
differ significantly between the HIV-positive and HIV-negative men.
Incidence of progression to AIN3 was 8.1
per 100 person-years. Incidence differed according to HIV status and was
significantly higher among the HIV-positive participants (13.1 vs 4.5 per 100 person-years). Having an abnormal baseline
diagnosis (AIN1, AIN2) was associated with disease progression (p < 0.001).
Among the HIV-positive men, a nadir CD4 cell count below 200 cells/mm3
was a risk factor for progression to AIN3 (HR = 4.66; 95% CI, 1.65-13.11).
There were four new cases of anal cancer
during follow-up. Two people had HGAIN prior to their diagnosis with anal
cancer. The incidence rate of progression to anal cancer among participants with
HGAIN was 1.2 per 100 person-years.
The authors note that both incident anal
cancers occurred in HIV-positive people with a nadir CD4 cell count below 200
cells/mm3. “Our data support current guidelines that recommend any
abnormality on anal cytology warrants further investigation with HRA
[high-resolution anoscopy], as two of four incident anal cancers had only low
grade cytology a short time before the diagnosis of cancer,” observe the
There was a high rate of spontaneous
disease regression from HGAIN among the 101 people eligible for inclusion in
this analysis. Overall, 24% of participants experienced spontaneous improvement in
their disease, a regression incidence of 24 per 100 person-years. Biopsy showed
that most of these people (71%) regressed to AIN1, the other 29% being
totally free of any disease.
Spontaneous regression from AIN3 was
observed in 26 (47%) of the 55 participants included in this analysis. Overall,
these people contributed 38 person-years of follow-up, and the incidence of
regression was 69 per 100 person-years. Rates of regression were similar
between the HIV-positive and HIV-negative men.
“High-grade ASILs frequently spontaneously
regressed,” conclude the authors. “Prospective studies to delineate risk
factors and biomarkers that predict those at highest risk of progression to
cancer are needed so that intervention can be targeted, and avoided in those
for whom it is unlikely to be of value.”